Pregnancy Outcomes in Women With Thalassemia Trait: A Multicenter Cohort Study

Abstract

Introduction: Thalassemia trait generally has minimal clinical impact, but physiologic changes during pregnancy may increase the risk of anemia, transfusion requirements, and hypertensive disorders. Existing evidence on pregnancy outcomes in this population is limited, with some conflicting data. This study aims to evaluate pregnancy-related outcomes in patients with thalassemia trait using a large, multicenter database. Methods: For this retrospective cohort study, we used data from the TriNetX US Collaborative Network. Females aged 18–45 with ICD-10 codes indicating pregnancy (Z33.1, O00–O9A, Z34, or Z3A) were included. Patients with pregnancy and coexisting thalassemia trait (D56.3) were assigned to the thalassemia cohort (n = 22,913), while those without any thalassemia diagnosis comprised the nonthalassemia cohort (n = 5,611,147). Propensity score matching was performed to balance age, race/ethnicity, obesity, smoking status, essential hypertension, and Type 2 diabetes mellitus. After 1:1 matching, 22,770 patients remained in each cohort (total N = 45,540). Outcomes were assessed within 1 year of the index date, including anemia during pregnancy, blood transfusion, preeclampsia/eclampsia, cesarean delivery, venous thromboembolism (VTE), heart failure/cardiomyopathy, preterm delivery, intrauterine growth restriction (IUGR), and intrauterine fetal demise (IUFD). Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Results: Thalassemia trait was associated with higher risks of anemia during pregnancy (RR: 3.00 and 95% CI: 2.87–3.13), needing blood transfusion (RR: 1.90 and 95% CI: 1.69–2.20), preeclampsia/eclampsia (RR: 1.54 and 95% CI: 1.47–1.61), cesarean delivery (RR: 1.43 and 95% CI: 1.36–1.51), preterm delivery < 37 weeks (RR: 1.40 and 95% CI: 1.31–1.65), and IUGR (RR: 1.96 and 95% CI: 1.72–2.23), all were statistically significant with a p < 0.001. Increased risk was also observed for VTE (RR: 1.57 and 95% CI: 1.12–2.20, p < 0.001) and IUFD (RR: 1.37 and 95% CI: 1.087–1.75, p < 0.001). No significant association was found with heart failure/cardiomyopathy (RR: 1.28 and 95% CI: 0.93–1.76, p = 0.124). Conclusion: Thalassemia trait in pregnancy was associated with increased rates of anemia, transfusion, and adverse maternal and fetal outcomes. Such adverse outcomes include pre-eclampsia/eclampsia, cesarean delivery, preterm birth and IUGR. These findings underscore the need for tailored peripartum care strategies in this high-risk population.